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P2X<jats:sub>7<\/jats:sub>R is highly expressed on pro-inflammatory microglia and [<jats:sup>11<\/jats:sup>C]SMW139, a specific P2X<jats:sub>7<\/jats:sub>R tracer for positron emission tomography imaging, showed good pharmacokinetics, stability, and brain permeability in vivo. Our objective was to evaluate the potential of [<jats:sup>11<\/jats:sup>C]SMW139 for PET imaging of neuroinflammation in vivo in the experimental autoimmune encephalomyelitis (EAE) model.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>We induced EAE in Lewis rats by immunization with MBP 69-88 in complete Freund\u2019s adjuvant (CFA). We determined the affinity of [<jats:sup>11<\/jats:sup>C]SMW139 to human and rat P2X<jats:sub>7<\/jats:sub>R using saturation binding assay. Using this tracer, PET imaging was performed at the peak of disease and in the recovery phase. In vivo blocking experiments were conducted to validate the specific brain uptake of the tracer. Immunohistochemistry staining and autoradiography were performed to evaluate the level of neuroinflammation and validate the specific binding of [<jats:sup>11<\/jats:sup>C]SMW139.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>[<jats:sup>11<\/jats:sup>C]SMW139 showed good affinity for the rat P2X<jats:sub>7<\/jats:sub>R with a K<jats:sub>d<\/jats:sub> of 20.6\u2009\u00b1\u20091.7\u00a0nM. The uptake of [<jats:sup>11<\/jats:sup>C]SMW139 was significantly higher in EAE animals at the peak of disease compared to the recovery phase but not in CFA control animals. The amplitude of increase of [<jats:sup>11<\/jats:sup>C]SMW139 uptake showed significant positive correlation with clinical scores mainly in the spinal cord (Pearson\u2009=\u20090.75, Spearman\u2009=\u20090.76; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Treating EAE animals with P2X<jats:sub>7<\/jats:sub>R antagonist JNJ-47965567 blocked the uptake of [<jats:sup>11<\/jats:sup>C]SMW139 in the spinal cord, cerebellum, and brain stem, demonstrating specific accumulation of the tracer. P-glycoprotein blocking with tariquidar (30\u00a0mg\/kg) did not affect tracer penetration in the brain showing that [<jats:sup>11<\/jats:sup>C]SMW139 is not a Pgp substrate.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Our data shows that [<jats:sup>11<\/jats:sup>C]SMW139 is a promising PET tracer for imaging neuroinflammation and evaluating the dynamics of pro-inflammatory microglia in the brain. This can provide crucial insights into the role of microglia in disease progression and enables the development of novel treatment strategies aimed at modulating the immune response in order to promote neuroprotection.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12974-020-01962-7","type":"journal-article","created":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T11:02:56Z","timestamp":1602673376000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["PET imaging of P2X7R in the experimental autoimmune encephalomyelitis model of multiple sclerosis using [11C]SMW139"],"prefix":"10.1186","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2216-4439","authenticated-orcid":false,"given":"Wissam","family":"Beaino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bieneke","family":"Janssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Kooijman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Vos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Schuit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"O\u2019Brien-Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kassiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert","family":"van het Hof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle J.","family":"Vugts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helga E.","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert D.","family":"Windhorst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,14]]},"reference":[{"key":"1962_CR1","doi-asserted-by":"publisher","first-page":"e00362","DOI":"10.1002\/brb3.362.","volume":"5","author":"N Garg","year":"2015","unstructured":"Garg N, Smith TW. 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